We propose three sets of studies of the expression of oral lesions by HIV-infected people, varing from molecular epidemiology to traditional epidemiology. These analyses will be based on six cohort studies and one clinic population; three cohorts follow subjects from seroconversion (Tricontinental Seroconverter Study, HIVNET, and a subset of the S.F. Men's Health Study). The study populations include adolescents, women and men, who were infected with HIV through sex or injection drug use. Currently, both HIV viral load and oral lesions are being used as outcome measures in clinical trials of antiretroviral treatments, however, the relationship between these outcomes has not been characterized. Under Aim 1 we will study this relationship in three cohorts whose viral load is being measured serially. If we demonstrate a strong association, then the usefulness of oral lesions as markers of disease progression is enhanced, in part because periodic clinical examinations are far less expensive than viral load assays. The prognostic value of oral lesions for progression of HIV disease has led to their use in defining the CDC classification of HIV disease and prophylaxes for PCP. Much of this research has been based on cohorts of homosexual/bisexual men, some of which has not distinguished between types of oral lesions. We have observed striking differences in prevalence of lesion types by risk group, which may have implications for their role in clinical trails and as bases for therapeutic management of HIV disease. Under Aim 2 we continue our studies of the incidence, prognostic value, and risk factors of oral lesions by risk group. Clinicians increasingly are reporting cases of azole resistance among HIV-infected subjects with very low CD4 counts. Resistance arising through replacement of a susceptible isolate with a resistant isolate from a different species raises the question of the role of person-to-person transmission and the potential for prevention of primary infection. Under Aim 3 we propose to conduct a case-control of azole-resistant candidiasis with DNA fingerprinting of isolates using the Ca2 probe.